tbuckley/cabot-search huggingface dataset:
Effectiveness of Fecal Microbiota Transplantation for Weight Loss in Patients With Obesity Undergoing Bariatric Surgery
Authors: Perttu Lahtinen, Anne Juuti, Markku Luostarinen, Leo Niskanen, Tarja Liukkonen, Jyrki Tillonen, Jyrki Kössi, Vesa Ilvesmäki, Mikko Viljakka, Reetta Satokari, Perttu Arkkila
Journal: JAMA Network Open (2022)

Importance Severe obesity is a major health concern. However, a few patients remain resistant to bariatric surgery and other treatments. Animal studies suggest that weight may be altered by fecal microbiota transplantation (FMT) from a lean donor. Objective To determine whether FMT from a lean donor reduces body weight and further improves the results of bariatric surgery. Design, Setting, and Participants This double-blinded, placebo-controlled, multicenter, randomized clinical trial was conducted in 2018 to 2021 among adult individuals with severe obesity treated at 2 bariatric surgery centers in Finland and included 18 months of follow-up. Patients eligible for bariatric surgery were recruited for the study. Data were analyzed from March 2021 to May 2022. Interventions FMT from a lean donor or from the patient (autologous placebo) was administered by gastroscopy into the duodenum. Bariatric surgery was performed 6 months after the baseline intervention using laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) Main Outcomes and Measures The main outcome was weight reduction measured as the percentage of total weight loss (TWL). Results Forty-one patients were recruited to participate in the study and were included in the final analysis (29 women [71.1%]; mean [SD] age, 48.7 [8.7] years; mean [SD] body mass index, 42.5 [6.0]). A total of 21 patients received FMT from a lean donor, and 20 received an autologous placebo. Six months after FMT, 34 patients underwent LRYGB and 4 underwent LSG. Thirty-four patients (82.9%) attended the last visit 18 months after the baseline visit. The percentage of TWL at 6 months was 4.8% (95% CI, 2.7% to 7.0%; P &amp;amp;lt; .001) in the FMT group and 4.6% (95% CI, 1.5% to 7.6%; P = .006) in the placebo group, but no difference was observed between the groups. At 18 months from the baseline (ie, 12 months after surgery), the percentage of TWL was 25.3% (95% CI, 19.5 to 31.1; P &amp;amp;lt; .001) in the FMT group and 25.2% (95% CI, 20.2 to 30.3; P &amp;amp;lt; .001) in the placebo group; however, no difference was observed between the groups. Conclusions and Relevance FMT did not affect presurgical and postsurgical weight loss. Further studies are needed to elucidate the possible role of FMT in obesity. Trial Registration ClinicalTrials.gov Identifier: NCT03391817
Associations of Greenness, Parks, and Blue Space With Neurodegenerative Disease Hospitalizations Among Older US Adults
Authors: Jochem O. Klompmaker, Francine Laden, Matthew H. E. M. Browning, Francesca Dominici, Marcia P. Jimenez, S. Scott Ogletree, Alessandro Rigolon, Antonella Zanobetti, Jaime E. Hart, Peter James
Journal: JAMA Network Open (2022)

Importance Exposure to natural environments has been associated with health outcomes related to neurological diseases. However, the few studies that have examined associations of natural environments with neurological diseases report mixed findings. Objective To evaluate associations of natural environments with hospital admissions for Alzheimer disease and related dementias (ADRD) and Parkinson disease (PD) among older adults in the US. Design, Setting, and Participants This open cohort study included fee-for-service Medicare beneficiaries aged 65 years or older who lived in the contiguous US from January 1, 2000, to December 31, 2016. Beneficiaries entered the cohort on January 1, 2000, or January 1 of the year after enrollment. Data from US Medicare enrollment and Medicare Provider Analysis and Review files, which contain information about individual-level covariates and all hospital admissions for Medicare fee-for-service beneficiaries, were analyzed between January 2021 and September 2022. Exposures Differences in IQRs for zip code–level greenness (normalized difference vegetation index [NDVI]), percentage park cover, and percentage blue space cover (surface water; ≥1.0% vs &amp;amp;lt;1.0%). Main Outcomes and Measures The main outcome was first hospitalizations with a primary or secondary discharge diagnosis of ADRD or PD. To examine associations of exposures to natural environments with ADRD and PD hospitalization, we used Cox-equivalent Poisson models. Results We included 61 662 472 and 61 673 367 Medicare beneficiaries in the ADRD and PD cohorts, respectively. For both cohorts, 55.2% of beneficiaries were women. Most beneficiaries in both cohorts were White (84.4%), were not eligible for Medicaid (87.6%), and were aged 65 to 74 years (76.6%) at study entry. We observed 7 737 609 and 1 168 940 first ADRD and PD hospitalizations, respectively. After adjustment for potential individual- and area-level confounders (eg, Medicaid eligibility and zip code–level median household income), NDVI was negatively associated with ADRD hospitalization (hazard ratio [HR], 0.95 [95% CI, 0.94-0.96], per IQR increase). We found no evidence of an association of percentage park and blue space cover with ADRD hospitalization. In contrast, NDVI (HR, 0.94 [95% CI, 0.93-0.95], per IQR increase), percentage park cover (HR, 0.97 [95% CI, 0.97-0.98], per IQR increase), and blue space cover (HR, 0.97 [95% CI, 0.96-0.98], ≥1.0% vs &amp;amp;lt;1.0%) were associated with a decrease in PD hospitalizations. Patterns of effect modification by demographics differed between exposures. Conclusions and Relevance The findings of this cohort study suggest that some natural environments are associated with a decreased risk of ADRD and PD hospitalization.
Association Between Doses of Levonorgestrel Intrauterine Systems and Subsequent Use of Psychotropic Drugs in France
Authors: Noémie Roland, Bérangère Baricault, Alain Weill, Kim Bouillon, Rosemary Dray-Spira, Lise Duranteau, Mahmoud Zureik
Journal: JAMA (2022)

This matched-cohort study uses data from the French National Health Insurance database to assess whether a 19.5-mg levonorgestrel intrauterine system, vs a 52-mg system, is associated with increased use of antidepressant, hypnotic, and anxiolytic medications.
The tetraspanin CD53 protects stressed hematopoietic stem cells via promotion of DREAM complex–mediated quiescence
Authors: Zev J. Greenberg, Luana Chiquetto Paracatu, Darlene A. Monlish, Qian Dong, Michael Rettig, Nate Roundy, Rofaida Gaballa, Weikai Li, Wei Yang, Cliff J. Luke, Laura G. Schuettpelz
Journal: Blood (2022)

Abstract The hematopoietic stem cell (HSC) cycle responds to inflammatory and other proliferative stressors; however, these cells must quickly return to quiescence to avoid exhaustion and maintain their functional integrity. The mechanisms that regulate this return to quiescence are not well understood. Here, we show that tetraspanin CD53 is markedly upregulated in HSCs in response to a variety of inflammatory and proliferative stimuli and that the loss of CD53 is associated with prolonged cycling and reduced HSC function in the context of inflammatory stress. Mechanistically, CD53 promotes the activity of the dimerization partner, RB-like, E2F, and multi-vulva class B (DREAM) transcriptional repressor complex, which downregulates genes associated with cycling and division. Proximity labeling and confocal fluorescence microscopy studies showed that CD53 interacts with DREAM-associated proteins, specifically promoting the interaction between Rbl2/p130 and its phosphatase protein phosphatase 2A (PP2A), effectively stabilizing p130 protein availability for DREAM binding. Together, these data identified a novel mechanism by which stressed HSCs resist cycling.
More Evidence of the Association of Depression With Adherence to Medical Therapies in Coronary Heart Disease
Authors: Robert M. Carney
Journal: JAMA Network Open (2022)

Matthew E. Lapa, MD; Gretchen M. Swabe, MS; Bruce L. Rollman, MD; Matthew F. Muldoon, MD; Rebecca C. Thurston, PhD; Jared W. Magnani, MD, MSc
Bariatric surgery for non-alcoholic fatty liver disease: Indications and post-operative management
Authors: Anja Geerts, Sander Lefere
Journal: Clinical and Molecular Hepatology (2022)

The prevalence of obesity and metabolic consequences such as nonalcoholic fatty liver diseases (NAFLD) has become a crucial health problem. Lifestyle modifications, especially weight loss, effectively reduces liver injury in NAFLD patients. However, adherence to lifestyle changes is very low in the clinical setting. Bariatric surgery can improve metabolic components and cause long-term weight loss. Therefore, bariatric surgery could serve as an attractive treatment option for NAFLD patients. This review integrates data about the benefits of bariatric surgery on NAFLD but also describes the potential pitfalls.
Validation of different personalized risk models of chemotherapy‐induced nausea and vomiting: results of a randomized, double‐blind, phase III trial of fosaprepitant for cancer patients treated with high‐dose cisplatin
Authors: Yuanyuan Zhao, Bing Zhao, Gang Chen, Yinlan Chen, Zijun Liao, Haiming Zhang, Weineng Feng, Yinyin Li, Heng Weng, Weidong Li, Yuefen Zhou, Biyong Ren, Yanda Lu, Jianhua Chen, Zhenteng Liu, Zhenzhong Su, Wenliang Wang, Li Zhang
Journal: Cancer Communications (2022)

Abstract Background Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis. The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant‐based triple antiemetic regimen for the prevention of chemotherapy‐induced nausea and vomiting (CINV) in patients with solid malignant tumors, determine risk factors and externally validate different personalized risk models for CINV. Methods This phase III trial was designed to test the non‐inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single‐day cisplatin chemotherapy. The primary endpoint was complete response (CR) during the overall phase (OP) with a non‐inferiority margin of 10.0%. Logistic regression models were used to assess the risk factors of CR and no nausea. To validate the personalized risk models, the accuracy of the risk scoring systems was determined by measuring the specificity, sensitivity and area under the receiver operating characteristic (ROC) curve (AUC), while the predictive accuracy of the nomogram was measured using concordance index (C‐index). Results A total of 720 patients were randomly assigned. CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group (78.1% vs. 77.7%, P = 0.765) with a between‐group difference of 0.4% (95% CI, ‐5.7% to 6.6%). Female sex, higher cisplatin dose (≥ 70 mg/m 2 ), no history of drinking and larger body surface area (BSA) were significantly associated with nausea. The AUC for the acute and delayed CINV risk indexes was 0.68 (95% CI: 0.66‐0.71) and 0.66 (95% CI: 0.61‐0.70), respectively, and the C‐index for nomogram CINV prediction was 0.59 (95% CI, 0.54‐0.64). Using appropriate cutoff points, the three models could stratify patients with high‐ or low‐risk CINV. No nausea and CR rate were significantly higher in the low‐risk group than in the high‐risk group ( P &lt; 0.001). Conclusions Fosaprepitant‐based triple prophylaxis demonstrated non‐inferior control for preventing CINV in patients treated with cisplatin‐base chemotherapy. Female cancer patients without a history of alcohol consumption, with larger BSA and received high‐dose cisplatin might be more vulnerable to CINV. Three personalized prediction models were well‐validated and could be used to optimize antiemetic therapy for individual patients.
Sotorasib in <i>KRAS</i> p.G12C–Mutated Advanced Pancreatic Cancer
Authors: John H. Strickler, Hironaga Satake, Thomas J. George, Rona Yaeger, Antoine Hollebecque, Ignacio Garrido-Laguna, Martin Schuler, Timothy F. Burns, Andrew L. Coveler, Gerald S. Falchook, Mark Vincent, Yu Sunakawa, Laetitia Dahan, David Bajor, Sun-Young Rha, Charlotte Lemech, Dejan Juric, Marko Rehn, Gataree Ngarmchamnanrith, Pegah Jafarinasabian, Qui Tran, David S. Hong
Journal: New England Journal of Medicine (2022)

KRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy of sotorasib, a KRAS G12C inhibitor, in previously treated patients with KRAS p.G12C–mutated pancreatic cancer are unknown.
Outbreak of SARS-CoV-2 Omicron Infection in a Centralized Quarantine Location in Hangzhou, China
Authors: Hexiang Jia, Yongtao Zheng, Yuxin Jia, Chenyang Jin, Yingjian Wang, Jiaqin Zhuang, Yang Ge
Journal: JAMA Network Open (2022)

This cohort study assesses whether transmission of COVID-19 occurred among individuals staying on different floors at a hotel used as a centralized quarantine location in Hangzhou, China.
Long-term Incidence Rates of Esophageal Squamous Cell Carcinoma in Chinese Patients With Low-grade Intraepithelial Neoplasia and Association of Surveillance Endoscopy With Incidence
Authors: He Li, Hongliang Wu, Maomao Cao, Yiwen Yu, Jinyi Zhou, Shaokai Zhang, Feng Tong, Jiyong Gong, Huadong Wang, Fan Yang, Siyi He, Xinxin Yan, Shaoli Zhang, Pengfei Luo, Hengmin Ma, Ling Liang, Changfa Xia, Wanqing Chen
Journal: JAMA Network Open (2022)

Importance Surveillance endoscopy is recommended for patients with low-grade intraepithelial neoplasia (LGIN); high-quality evidence about the use of surveillance endoscopy and esophageal squamous cell carcinoma (ESCC) incidence in patients with LGIN is important but limited. Objective To estimate long-term ESCC incidence rates in patients with LGIN and the association between surveillance endoscopy and ESCC incidence. Design, Setting, and Participants This community-based, multicenter, prospective cohort study in 9 regions in rural China included patients with LGIN diagnosed by endoscopic screening between July 1, 2007, and December 31, 2016; all participants were followed up until December 31, 2021. Main Outcomes and Measures The primary outcome was ESCC incidence. The ESCC standardized incidence ratio (SIR) was estimated using sex- and age-specific incidence in the general population of rural China in 2010 and hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Results A total of 3258 patients with LGIN were included; 1772 (54.39%) were men, with a mean (SD) age of 58.21 (6.97) years. Among them, 1378 patients (42.30%) underwent at least 1 surveillance endoscopy (surveillance group) and 1880 (57.70%) did not undergo any surveillance endoscopy (nonsurveillance group). During the follow-up period (median, 7.96 years; IQR, 6.08-10.54 years), 170 ESCC cases were diagnosed, with a cumulative incidence of 6.28 per 1000 person-years. A higher incidence of ESCC (incidence rate, 7.07 per 1000 person-years) was observed in the nonsurveillance group than in the surveillance group (incidence rate, 5.14 per 1000 person-years). Patients with LGIN in the surveillance group had a lower SIR (SIR, 4.07; 95% CI, 1.13-10.34) than those in the nonsurveillance group (SIR, 5.65; 95% CI, 2.00-12.58); however, patients with LGIN in both groups had a higher risk of ESCC than the general population. Patients in the surveillance group had a 31% decreased risk of ESCC incidence (HR, 0.69; 95% CI, 0.50-0.95) compared with those in the nonsurveillance group, after adjusting for baseline risk factors. Conclusions and Relevance In this prospective cohort study, patients with LGIN had a higher risk of developing ESCC than the general population, and endoscopic surveillance was associated with a decrease in ESCC incidence in these patients.
A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk
Authors: Antje K. Rottner, Yingying Ye, Elena Navarro-Guerrero, Varsha Rajesh, Alina Pollner, Romina J. Bevacqua, Jing Yang, Aliya F. Spigelman, Roberta Baronio, Austin Bautista, Soren K. Thomsen, James Lyon, Sameena Nawaz, Nancy Smith, Agata Wesolowska-Andersen, Jocelyn E. Manning Fox, Han Sun, Seung K. Kim, Daniel Ebner, Patrick E. MacDonald, Anna L. Gloyn
Journal: Nature Genetics (2022)

Identification of the genes and processes mediating genetic association signals for complex diseases represents a major challenge. As many of the genetic signals for type 2 diabetes (T2D) exert their effects through pancreatic islet-cell dysfunction, we performed a genome-wide pooled CRISPR loss-of-function screen in a human pancreatic beta cell line. We assessed the regulation of insulin content as a disease-relevant readout of beta cell function and identified 580 genes influencing this phenotype. Integration with genetic and genomic data provided experimental support for 20 candidate T2D effector transcripts including the autophagy receptor CALCOCO2. Loss of CALCOCO2 was associated with distorted mitochondria, less proinsulin-containing immature granules and accumulation of autophagosomes upon inhibition of late-stage autophagy. Carriers of T2D-associated variants at the CALCOCO2 locus further displayed altered insulin secretion. Our study highlights how cellular screens can augment existing multi-omic efforts to support mechanistic understanding and provide evidence for causal effects at genome-wide association studies loci.
A liquid biopsy signature of circulating exosome-derived mRNAs, miRNAs and lncRNAs predict therapeutic efficacy to neoadjuvant chemotherapy in patients with advanced gastric cancer
Authors: Ting Guo, Xiao-Huan Tang, Xiang-Yu Gao, Yuan Zhou, Bo Jin, Zi-Qian Deng, Ying Hu, Xiao-Fang Xing, Zi-Yu Li, Jia-Fu Ji
Journal: Molecular Cancer (2022)

At present, there is no validated marker to identify the subpopulation of patients with advanced gastric cancer (AGC) who might benefit from neoadjuvant chemotherapy (NACT). In view of this clinical challenge, the identification of non-invasive biomarkers for efficacy prediction of NACT in patients with AGC is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy-based assay by using an exosome-derived RNAs model based on multi-omics characteristics of RNAs. We firstly used a multi-omics strategy to characterize the mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) profiles of circulating exosome enriched fractions in responders to NACT paired with non-responders, using RNA sequencing. Finally, numerous miRNAs, mRNAs and lncRNAs were identified to be associated with the response to NACT in patients with AGC, and it was validated in an independent cohort with promising AUC values. Furthermore, we established a 6-exosome-RNA panel that could robustly identified responders from non-responders treated with fluorouracil-based neoadjuvant chemotherapy.
Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003
Authors: Rita W. Y. Ng, Siaw S. Boon, Zigui Chen, Wendy C. S. Ho, Kitty S. C. Fung, Barry K. C. Wong, Apple C. M. Yeung, Martin C. S. Wong, Paul K. S. Chan
Journal: JAMA Network Open (2022)

Importance Knowledge of the longevity and breath of immune response to coronavirus infection is crucial for the development of next-generation vaccines to control the COVID-19 pandemic. Objectives To determine the profile of SARS-CoV-2 antibodies among persons infected with the closely related virus, SARS-CoV-1, in 2003 (SARS03 survivors) and to characterize their antibody response soon after the first and second doses of COVID-19 vaccines. Design, Setting, and Participants This prospective cohort study examined SARS-CoV-2 antibodies among SARS03 survivors compared with sex- and age-matched infection-naive controls. Participants received the COVID-19 vaccines between March 1 and September 30, 2021. Interventions One of the 2 COVID-19 vaccines (inactivated [CoronaVac] or messenger RNA [BNT162b2]) available in Hong Kong. Two doses were given according to the recommended schedule. The vaccine type administered was known to both participants and observers. Main Outcomes and Measures SARS-CoV-2 antibodies were measured prevaccination, 7 days after the first dose, and 14 days after the second dose. Results Eighteen SARS03 adult survivors (15 women and 3 men; median age, 46.5 [IQR, 40.0-54.3] years) underwent prevaccination serologic examination. The vast majority retained a detectable level of antibodies that cross-reacted with SARS-CoV-2 (16 of 18 [88.9%] with nucleocapsid protein antibodies and 17 of 18 [94.4%] with receptor-binding domain of spike protein antibodies); a substantial proportion (11 of 18 [61.1%]) had detectable cross-neutralizing antibodies. Twelve SARS03 adult survivors (10 women and 2 men) underwent postvaccination serologic examination. At 7 days after the first dose of vaccine, SARS03 survivors mounted significantly higher levels of neutralizing antibodies compared with controls (median inhibition: 89.5% [IQR, 77.1%-93.7%] vs 13.9% [IQR, 11.8%-16.1%] for BNT162b2; 64.9% [IQR, 60.8%-69.5%] vs 13.4% [IQR, 9.5%-16.8%] for CoronaVac; P &amp;amp;lt; .001 for both). At 14 days after the second dose, SARS03 survivors generated a broader antibody response with significantly higher levels of neutralizing antibodies against variants of concern compared with controls (eg, median inhibition against Omicron variant, 52.1% [IQR, 35.8%-66.0%] vs 14.7% [IQR, 2.5%-20.7%]; P &amp;amp;lt; .001). Conclusions and Relevance The findings of this prospective cohort study suggest that infection with SARS-CoV-1 was associated with detectable levels of antibodies that cross-react and cross-neutralize SARS-CoV-2, which belongs to a distinct clade under the same subgenus Sarbecovirus . These findings support the development of broadly protective vaccines to cover sarbecoviruses that caused 2 devastating zoonotic outbreaks in humans over the last 2 decades.
A polygenic score for reduced kidney function and adverse outcomes in a cohort with chronic kidney disease
Authors: Inga Steinbrenner, Zhi Yu, Jin Jin, Ulla T. Schultheiss, Fruzsina Kotsis, Morgan E. Grams, Josef Coresh, Matthias Wuttke, Florian Kronenberg, Kai-Uwe Eckardt, Nilanjan Chatterjee, Peggy Sekula, Anna Köttgen
Journal: Kidney International (2022)

Chronic kidney disease (CKD) is a global health burden of increasing importance that affects >10% of the general adult population.1 CKD is defined as the sustained presence of abnormalities of kidney structure or function, and it is classified using estimated glomerular filtration rate (eGFR) and the urinary albumin-to-creatinine ratio.S1 The eGFR based on serum creatinine is the most common measure of kidney function. Persons with CKD are at increased risk of adverse outcomes, such as kidney failure (KF), cardiovascular diseases, and premature death.
ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment
Authors: Javiera Villar, Adeline Cros, Alba De Juan, Lamine Alaoui, Pierre-Emmanuel Bonte, Colleen M. Lau, Ioanna Tiniakou, Boris Reizis, Elodie Segura
Journal: Nature Immunology (2022)

Abstract In inflamed tissues, monocytes differentiate into macrophages (mo-Macs) or dendritic cells (mo-DCs). In chronic nonresolving inflammation, mo-DCs are major drivers of pathogenic events. Manipulating monocyte differentiation would therefore be an attractive therapeutic strategy. However, how the balance of mo-DC versus mo-Mac fate commitment is regulated is not clear. In the present study, we show that the transcriptional repressors ETV3 and ETV6 control human monocyte differentiation into mo-DCs. ETV3 and ETV6 inhibit interferon (IFN)-stimulated genes; however, their action on monocyte differentiation is independent of IFN signaling. Instead, we find that ETV3 and ETV6 directly repress mo-Mac development by controlling MAFB expression. Mice deficient for Etv6 in monocytes have spontaneous expression of IFN-stimulated genes, confirming that Etv6 regulates IFN responses in vivo. Furthermore, these mice have impaired mo-DC differentiation during inflammation and reduced pathology in an experimental autoimmune encephalomyelitis model. These findings provide information about the molecular control of monocyte fate decision and identify ETV6 as a therapeutic target to redirect monocyte differentiation in inflammatory disorders.